The meldonium conundrum

Has WADA thrown a lifeline to athletes who have turned in positive tests for meldonium as has been widely reported? Or is there a meldonium-linked amnesty as is being suggested by certain people and being debated in the international media?

Can Maria Sharapova greatly benefit_or benefit at all_from the latest clarification by WADA regarding ‘excretion times’ for the drug that was brought into international focus on March 7 last when the Russian tennis star announced that she had tested positive for the little-known cardiac drug?

These questions are being raised and discussed across the world following WADA’s fresh guidelines for pursuing the meldonium doping cases. The meldonium infractions have risen to 201 as on April 15. The numbers are unprecedented for a single drug within a four-month span of its inclusion in the banned list.

Unprecedented intervention

WADA’s intervention in such a short period of time after a drug being introduced into the Prohibited List, with detailed clarifications regarding thresholds to be pursued or ignored for a non-threshold substance is also unprecedented.

With some of the athletes and organizations questioning the ‘excretion times’ of the drug, perhaps WADA perforce had to step in and issue guidelines which has led to speculation about the basis of its inclusion in the Prohibited List as well as about the “escape route” that the “guidance” may provide to at least some of the athletes. WADA stated that several anti-doping agencies were seeking guidance and because of the “unprecedented situation” created by meldonium it felt the need to provide “additional guidance for the anti-doping community.”

Ukrainian athlete Nataliya Lupu was one of the earliest among the meldonium offenders to claim that even after stopping the drug a good two months ahead of the January 1 deadline, she had tested positive. She stated that she had been taking the drug for the past 15 years for medical reasons and thought she had stopped well in time to prevent a ‘positive’. It was the second doping offence for the former European indoor 800m champion.  She was withdrawn from the World Indoor Championships in Portland, US.

In the third week of March Russian middle distance runner Andrey Minzhulin made the claim that the Prohibited List was translated into Russian only in October 2015 and if the drug was taking as much as 100 days to clear from the system (as was being claimed at that time) then it would be unfair to penalize athletes if they tested positive in January 2016.

Manufacturer's claim

Around the same time, Grindeks, the manufacturer of meldonium, told Reuters that the drug had a half -life of four to six hours but “its terminal elimination from the body may last for several months”. (Half-life means the time it takes to reduce the concentration of a drug in the body by half).

WADA has now conceded in its note to anti-doping agencies that meldonium may remain in the system for “a few months”. It has issued concentration levels that could be considered for different periods. The fundamental rationale is if an athlete is claiming that he or she took the drug in October-November there is still a possibility of a positive test in January and the athlete deserves the benefit of some concession.

The cut-off of 1 to 15 microgram/ml stipulated for samples collected before March 1 may not, however, be too encouraging for those trying to find a way out if they had committed an offence. Nor would the 1mcg/ml (0.000001g/ml) limit given for tests done after March 1.

“In the case of meldonium, there is currently a lack of clear scientific information on excretion times. For this reason, a hearing panel might justifiably find (unless there is specific evidence to the contrary) that an athlete who has established on the balance of probabilities that he or she ingested meldonium before 1 January 2016 could not reasonably have known or suspected that the meldonium would still be present in his or her body on or after 1 January 2016. In these circumstances, WADA considers that there may be grounds for no fault or negligence on the part of the athlete” WADA notice stated.

“Based on the preliminary results of the aforementioned studies, this translates to urinary concentrations higher than 10 μg/mL up to 72 h (first elimination phase), followed by a persistent long-term excretion (second elimination phase) yielding concentrations up to approximately 2 μg/mL over the following three weeks. Long term urinary excretion below 1 μg/mL down to several hundred ng/mL can persist for a number of weeks and in the low tens of ng/mL for a few months,” WADA said. (1ng=000000001g).
WADA has recommended that proceedings may be continued if the concentration is above 15 mcg/ml since it would suggest recent intake of the drug. 

No blanket amnesty

This is not a blanket amnesty. It may turn out to be a lifeline for some of the offenders. It is difficult to guess what those numbers could be from among the 200-odd meldonium positive cases reported so far. Already at least 14 athletes in Russia and Georgia have had their provisional suspensions lifted because of the guidelines issued by WADA. There could be more that had not been reported.

Those who might have ingested the drug prior to January 1 and concentration levels show below 1mcg/ml would be reprieved when the hearing process begins. Their provisional suspensions would be lifted straightaway. Meldonium being a 'non-specified'drug a provisional suspension was standard. Because of the uncertainty over éxcretion times' WADA has now given anti-doping authorities the right to lift the provisional suspension in case ingestion prior to Jan 1 is firmly indicated.

The final decision on all these cases would be dependent on the outcome of the ongoing ‘excretion studies' which alone would be able to determine with some measure of certainty when the athlete would have taken the banned drug. The studies may well be challenged scientifically and legally.

“Cases where the concentration is below 1 μg/ml and the test was taken before 1 March 2016 are compatible with an intake prior to January 2016. If the anti-doping organization finds that the athlete could not reasonably have known or suspected that the substance would still be present in his/her body on or after 1 January 2016, then a finding of no fault or negligence may be made."

At this point all these could be sounding rather confusing. But once the hearing process begins and news gets out, we would be in a position to understand the implications of this WADA notice in a better way.

Sharapova's case

How much of an advantage Maria Sharapova might have following the latest WADA notice?

None perhaps!

The International Tennis Federation (ITF) has stated that it had taken note of the WADA notice and it would go ahead with a hearing for the superstar. The Russian tennis star’s provisional suspension has not been lifted, an indication as to how the fresh guidelines would have worked in her case.

Sharapova did not say she knew the substance was banned and had made sure that she stopped taking meldonium_prescribed to her by her family doctor for an ostensible cardiac condition 10 years ago_in October or November. On the contrary she told the media that she did not know meldonium was banned. No one had told her and she missed clicking a link in a WADA communication that could have given her the crucial information.

She did not say when she took it last. But as things turned out, one of her sponsors, tennis racquet manufacturer, Head, issued a statement on March 11 which stated, among other things:

“On this basis we conclude that although it is beyond doubt that she tested positive for the use of a WADA banned substance, the circumstantial evidence is equally beyond doubt that the continued use of meldonium after Jan 1st, 2016 in the dosages she had been recommended, which were significantly short of performance enhancing levels, was a manifest error by Maria. In the absence of any evidence of any intent by Maria of enhancing her performance or trying to gain an unfair advantage through the use of mildronate, we further conclude this falls into the category of 'honest' mistakes.”

The Head Chairman couldn’t have visualized how things would turn out when he issued the above statement.

WADA has said that in case an athlete admits that the substance was taken after 1 January or if there is “other evidence” that it was taken after 1 January, the proceedings would continue.

Can Sharapova now disown the statement by Head Chairman and CEO, Johan Eliasch, that the she was taking meldonium in small quantities even after January 1? It looks doubtful whether such an argument could be made convincingly before a hearing panel.

Much would depend on the concentration levels being returned in their urine samples by individual athletes including Sharapova. Also the eventual outcome of the ‘excretion studies’ that the WADA-accredited laboratories are conducting at the moment. 
We should not forget the capabilities of the lawyers who would be representing a majority of the athletes. This is a good season for lawyers, especially those who have the experience in anti-doping rule violation cases.

Efimova fails to get suspension lifted

With the Olympics getting closer there is understandable anxiety among athletes to get out of this “meldonium mess” and get on with competitions and qualification process.

One such athlete, Russian swimmer Yulia Efimova, 100m world breast-stroke champion, had tested positive for meldonium on a sample she provided last February. The US-based swimmer apparently told her coach that she had taken the drug last December.

However, as ill luck would have it (from her perspective) another test in January this year turned up negative, according to Swimvortex.

 Probably based on this evidence International Swimming Federation (FINA) has refused to lift her provisional suspension to enable her to compete in the Russian National Championships. Efimova, world number three, may still have an opportunity to make the Olympic selection if she is cleared of the doping charges. This is her second doping offence, she having served a suspension in 2013.

Just as the debate started about WADA’s wisdom of including meldonium in the Prohibited List immediately after the Sharapova bombshell, the latest WADA notice has triggered another round of arguments about how the agency goes about banning drugs.

People have called for conclusive evidence of performance-enhancement through clinical research before WADA includes any substance in the banned list. Russian President Vladimir Putin has gone to the extent of saying meldonium was never a performance-enhancing substance.

Critics and experts will continue to argue that WADA’s methods are arbitrary.

Inclusion of meldonium in Prohibited List

WADA, in the mantime, has stated: “The inclusion of meldonium on the 2016 Prohibited List concluded a long process conducted by the WADA List Committee between 2011 and 2015. This process, which included a review of the available scientific information and the generation of specific data (in particular via the 2015 Monitoring Program, which revealed a high prevalence of the use of meldonium by athletes and teams of athletes) ultimately led to the conclusion that meldonium met two of the three criteria listed at Article 4.3.1 of the World Anti-Doping Code (Code). In particular, claims of performance enhancement had been made by various authors, including the manufacturer of meldonium.”

The manufacturer, Grindeks, had of course denied when the focus shifted to it following the Sharapova announcement that meldonium was a performance-enhancer. Its inventor, Latvian Ivar Kalvins had also said, however, that he had developed the drug for use by Soviet troops in Afghanistan since operating in the mountains could result in lack of oxygen.

Is that not performance enhancing?

Someone will have to go to court to challenge the inclusion of meldonium or any other drug in the Prohibited List. WADA does not disclose all the selection criteria adopted for particular substances all the time. Nor has there been conclusive research about the performance-enhancing capacity of the hundreds of drugs listed by WADA. But it is always prepared to defend its decisions and in the case of meldonium it seems to have done its homework well enough barring of course the 'excretion' study.

One thing is clear, all of 200 athletes would not have been using meldonium either because they had cardiac problems or because they felt it was fashionable to use it. What could happen to it next year, without the controversy surrounding ‘excretion times’ is anybody’s guess.
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Click here for previous piece on meldonium.

(updated 18-04-2016)